Is MTM1 p.Pro330= (c.990T>C) pathogenic?

MTM1 p.Pro330= (c.990T>C) is classified Likely benign in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). Very rare (popmax 0.00218%, amr); Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Pro330= (c.990T>C)?

MTM1 p.Pro330= (c.990T>C) is associated with X-linked myotubular myopathy (ClinVar).

How common is MTM1 p.Pro330= (c.990T>C) in the general population?

MTM1 p.Pro330= (c.990T>C) is very rare (popmax 0.00218%, amr) (gnomAD).

How is X-linked centronuclear myopathy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTM1 p.Pro330=

c.990T>C · rs1557414127 · VCV2162090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Conditions

X-linked myotubular myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.68	GERP -4, phastCons 0.034
Overall
CADD	6.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00218% Admixed American · 1/45,974 alleles

Overall 8.27e-05% 1/1,209,603 alleles · very rare exomes 1/1,095,554 · genomes 0/114,049 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MTM1
Protein: p.Pro330=
Coding: c.990T>C
MANE Select: NM_000252
dbSNP: rs1557414127
Type: single nucleotide variant
Location: chrX:150649838 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 330: the myotubularin phosphatase domain

Full MTM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked myotubular myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked centronuclear myopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (France)

Similar variants

MTM1 p.Pro330Leu Uncertain significance ★ ⚠ same residue
MTM1 c.1644+1G>A Pathogenic ★★★ same condition
MTM1 p.Arg224Ter Pathogenic ★★★ same condition
MTM1 p.Arg69Cys Pathogenic ★★★ same condition
MTM1 p.Gln451= Likely pathogenic ★★★ same condition
MTM1 p.Glu404Lys Pathogenic ★★★ same condition
MTM1 p.Pro205Leu Pathogenic ★★★ same condition
MTM1 p.Trp230Arg Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mtm1-p-pro330 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown